Effects of gastrin-releasing peptide agonist and antagonist administered to the basolateral nucleus of the amygdala on conditioned fear in the rat

Rationale: Bombesin (BB)-like peptides have been shown to affect neuroendocrine and neural functions related to the stress response and the modulation of conditioned fear. In line with this view, central administration of gastrin-releasing peptide (GRP; a mammalian analogue of BB) or its receptor antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) BB^(6-14) (RC-3095) modulates conditioned fear. Objective: The present study examined the effects of bilateral infusions of GRP or its receptor antagonist (RC-3095) into the basolateral nucleus of the amygdala (BLA) on the conditioned emotional response. Methods: The effects of GRP (150, 300, and 600 ng/0.5 μl) and/or RC-3095 (50, 500, and 1,000 ng/0.5 μl) on contextual and cued fear conditioning were assessed following direct bilateral infusion of these compounds into the BLA. Results: Both GRP and RC-3095 (all doses) reduced freezing during the contextual testing period but did not influence responding in the cued test. Although both compounds reduced freezing in the contextual paradigms, at a moderate dose pretreatment with RC-3095 attenuated the GRP-elicited decrease in contextual freezing. Conclusions: It appears that manipulation of GRP at the BLA may influence the expression of learned fear and that these effects preferentially influence contextual versus cue-dependent emotional responses.